Radical Arylation Reactions of 4, 6, 8-Trimethylazulene

The synthesis of 1- and 2-aryl-substituted (aryl = Ph, 4-NO₂? C₆H₄, and 4-MeO? C₆H₄) 4, 6, 8-trimethylazulenes ( 4 and 3 , respectively) in moderate yields by direct arylation of 4, 6, 8-trimethylazulene ( 8 ) with the corresponding arylhydrazines 13 in the presence of Cu^IIions in pyridine (see Scheme 4) as well as with 4-MeO? C₆H₄Pb(OAc)₃ ( 16 ) in CF₃COOH (see Scheme 5) is described. With 13 , also small amounts of 1, 2- and 1, 3-diarylated azulenes (see 14 and 15 , respectively, in Scheme 4) are formed. The 4-methoxyphenylation of 8 with 16 yielded also the 1, 1′-biazulene 17 in minor amounts (see Scheme 5). 4, 6, 8-Trimethyl-2-phenylazulene ( 3a ) was also obtained as the sole product in moderate yields by the reaction of sodium phenylclopentadienide ( 1a ) with 2, 4, 6-trimethylpyrylium tetrafluoroborate ( 2 ) in THF (Scheme 1). The attempted phenylation of 8 as well as of azulene ( 9 ) itself with N-nitroso-N-phenylacetamide ( 10 ) led only to the formation of the corresponding 1-(phenylazo)-substituted azulenes 12 and 11 , respectively (Scheme 3).     

A Novel Approach towards 2,3,5-Trisubstituted Thiophenes via tandem Michael addition/intramolecular Knoevenagel condensation

Starting from the easily available, highly functionalized acetylenic ketories 4a–i (Scheme 1), novel 2,3,5-trisubstituted thiophenes 1a–i (Scheme 2) were synthesized in good yields using a tandem Michael-addition/intramolecular Knoevenagel-condensation strategy, featuring Cs₂CO₃/MgSO₄ (1:2) as an efficient base to effect the cyclization. Subsequent simple one-step transformations yielded 2,3-disubstituted thiophene-5-carbaidehydes 7a–c , carboxylic-acid derivatives 8, 9 , and 11 , and alcohol 10 (Scheme 3). These molecules constitute interesting novel thiophene-containing building blocks, useful for the preparation of low-molecular-weight compound libraries by combinatorial and parallel-chemistry techniques.     

Synthesis and Self‐Assembly of Bolaamphiphiles Based on β‐Amino Acids or an Alcohol

The synthesis of bolaamphiphiles from unusual β‐amino acids or an alcohol and C₁₂ or C₂₀ spacers is described. Unusual β‐amino acids such as a sugar amino acid, an AZT‐derived amino acid, a norbornene amino acid, and an AZT‐derived amino alcohol were coupled with spacers under standard conditions to get the novel bolaamphiphiles 5 – 8 (Scheme 1), 12 and 13 (Scheme 2), and 17 and 20 (Scheme 3). Some of these compounds, on precipitation from MeOH/H₂O, self‐assembled into organized molecular structures.     

New Results in the Synthesis of Styrylazulene Derivatives: Application of the ‘Anil synthesis’ to the preparation of azulenes substituted with styryl groups at the seven-membered ring

The synthesis of 4,6,8-trimethyl-1-[(E)-4-R-styryl]azulenes 5 (R=H, MeO, Cl) has been performed by Wittig reaction of 4,6,8-trimethylazulene-1-carbaldehyde ( 1 ) and the corresponding 4-(R-benzyl)(triphenyl)phosphonium chlorides 4 in the presence of EtONa/EtOH in boiling toluene (see Table 1). In the same way, guaiazulene-3-carbaldehyde ( 2 ) as well as dihydrolactaroviolin ( 3 ) yielded with 4a the corresponding styrylazulenes 6 and 7 , respectively (see Table 1). It has been found that 1 and 4b yield, in competition to the Wittig reaction, alkylation products, namely 8 and 9 , respectively (cf. Scheme 1). The reaction of 4,6,8-trimethylazulene ( 10 ) with 4b in toluene showed that azulenes can, indeed, be easily alkylated with the phosphonium salt 4b . 4,6,8-Trimethylazulene-2-carbaldehyde ( 12 ) has been synthesized from the corresponding carboxylate 15 by a reduction (LiAlH₄) and dehydrogenation (MnO₂) sequence (see Scheme 2). The Swern oxidation of the intermediate 2-(hydroxymethyl)azulene 16 yielded only 1,3-dichloroazulene derivatives (cf. Scheme 2). The Wittig reaction of 12 with 4a and 4b in the presence of EtONa/EtOH in toluene yielded the expected 2-styryl derivatives 19a and 19b , respectively (see Scheme 3). Again, the yield of 19b was reduced by a competing alkylation reaction of 19b with 4b which led to the formation of the 1-benzylated product 20 (see Scheme 3). The ‘anil synthesis’ of guaiazulene ( 21 ) and the 4-R-benzanils 22 (R=H, MeO, Cl, Me₂N) proceeded smoothyl under standard conditions (powered KOH in DMF) to yield the corresponding 4-[(E)-styryl]azulene derivatives 23 (see Table 4). In minor amounts, bis(azulen-4-yl) compounds of type 24 and 25 were also formed (see Table 4). The ‘anil reaction’ of 21 and 4-NO₂C₆H₄CH=NC₆H₅ ( 22e ) in DMF yielded no corresponding styrylazulene derivative 23e . Instead, (E)-1,2-bis(7-isopropyl-1-methylazulen-4-yl)ethene ( 27 ) was formed (see Scheme 4). The reaction of 4,6,8-trimethylazulene ( 10 ) and benzanil ( 22a ) in the presence of KOH in DMF yielded the benzanil adducts 28 to 31 (cf. Scheme 5). Their direct base-catalyzed transformation into the corresponding styryl-substituted azulenes could not be realized (cf. Scheme 6). However, the transformation succeeded smoothly with KOH in boiling EtOH after N-methylation (cf. Scheme 6).     

4-Amino-1,5-dihydro-2H-pyrrol-2-one aus Bortrifluorid-katalysierten Umsetzungen von 3-Amino-2H-azirinen mit Carbonsäure-Derivaten

4-Amino-1,5-dihydro-2H-pyrrol-2-ones from Boron Trifluoride Catalyzed Reactions of 3-Amino-2H-azirines with Carboxylic Acid Derivatives Reaction of 3-amino-2H-azirines 1 with ethyl 2-nitroacetate ( 6a ) in refluxing MeCN affords 4-amino-1,5-dihydro-2H-pyrrol-2-ones 7 and 3,6-diamino-2,5-dihydropyrazines 8 , the dimerization product of 1 (Scheme 2). Thus, 6a reacts with 1 as a CH-acidic compound by C? C bond formation via C-nucleophilic attack of deprotonated 6a onto the amidinium-C-atom of protonated 1 (Scheme 5). The scope of this reaction seems to be rather limited as 1 and 2-substituted 2-nitroacetates do not give any products besides the azirine dimer 8 (see Table 1). Sodium enolates of carboxylic esters and carboxamides 11 react with 1 under BF₃ catalysis to give 4-amino-1,5-dihydro-2H-pyrrol-2-ones 12 in 50–80% yield (Scheme 3, Table 2). In an analogous reaction, 3-amino-2H-pyrrole 13 is formed from 1c and the Li-enolate of acetophenone (Scheme 4). A reaction mechanism for the ring enlargement of 1 involving BF₃ catalysis is proposed in Scheme 6.     

Studies on Reactions of Thioketones with Trimethyl(trifluoromethyl)silane Catalyzed by Fluoride Ions

Treatment of 2,2,4,4‐tetramethylcyclobutane‐1,3‐dione ( 6 ) in THF with CF₃SiMe₃ in the presence of tetrabutylammonium fluoride (TBAF) yielded the corresponding 3‐(trifluoromethyl)‐3‐[(trimethylsilyl)oxy]cyclobutanone 7 (Scheme 1) via nucleophilic addition of a CF anion at the CO group and subsequent silylation of the alcoholate. Under similar conditions, the ‘monothione' 1 reacted to give thietane derivative 8 (Scheme 2), whereas in the case of ‘dithione' 2 only the dispirodithietane 9 , the dimer of 2 , was formed (Scheme 3). A conceivable mechanism for the formation of 8 is the ring opening of the primarily formed CF₃ adduct A followed by ring closure via the S‐atom (Scheme 2). In the case of thiobenzophenones 4 , complex mixtures of products were obtained including diarylmethyl trifluoromethyl sulfide 10 and 1,1‐diaryl‐2,2‐difluoroethene 11 (Scheme 4). Obviously, competing thiophilic and carbophilic addition of the CF anion took place. The reaction with 9H‐fluorene‐9‐thione ( 5 ) yielded only 9,9′‐bifluorenylidene ( 14 ; Scheme 6); this product was also formed when 5 was treated with TBAF alone. Treatment of 4a with TBAF in THF gave dibenzhydryl disulfide ( 15 ; Scheme 7), whereas, under similar conditions, 1 yielded the 3‐oxopentanedithioate 17 (Scheme 9). The reaction of dithione 2 with TBAF led to the isomeric dithiolactone 16 (Scheme 8), and 3 was transformed into 1,2,4‐trithiolane 18 (Scheme 10).     

Synthesis and Selected Reactions of Hydrazides Containing an Imidazole Moiety

The preparation of two types of imidazole derivatives bearing a hydrazide group was achieved by treatment of the corresponding esters with NH₂NH₂?H₂O in MeOH at room temperature. In the case of 4‐(ethoxycarbonyl)‐1H‐imidazole 3‐oxides 3 , hydrazides of type 1 were formed with retention of the N‐oxide structure (Scheme 1). Interestingly, due to a strong H‐bonding, no deoxygenation of the N→O function could be achieved even by treatment of 3 with Raney‐Ni. The second type, 2‐[(1H‐imidazol‐2‐yl)sulfanyl]acetohydrazides 2 , was obtained from 1H‐imidazole‐2(3H)‐thiones 4 in two steps via S‐alkylation with methyl bromoacetate, followed by treatment with NH₂NH₂?H₂O (Scheme 2). An imidazole 7 , containing both types of hydrazide groups, was prepared analogously from ethyl 2,3‐dihydro‐2‐thioxo‐1H‐imidazole‐4‐carboxylate 4d (Scheme 4). Both types of hydrazides, 1 and 2 , were transformed successfully to the corresponding acylhydrazones 8 and 9 , respectively (Scheme 5). Furthermore, it has been shown that hydrazides of type 1 are useful starting materials for the synthesis of 1,2,4‐triazole‐3‐thiones 11 and 1,3,4‐thiadiazole‐2‐amines 12 , bearing an imidazole 3‐oxide moiety (Scheme 7).     

Three-Component Reactions with Sterically Crowded 2,2,4,4-Tetramethyl-3-thioxocyclobutanone,Phenyl Azide,and Electron-Deficient C,C-Dipolarophiles

In order to trap ‘thiocarbonyl-aminides’ A , formed as intermediates in the reaction of thiocarbonyl compounds with phenyl azide, a mixture of 2,2,4,4-tetramethyl-3-thioxocyclobutanone ( 1 ), phenyl azide, and fumarodinitrile ( 8 ) was heated to 80° until evolution of N₂ ceased. Two interception products of the ‘thiocarbonylaminide’ A (Ar?Ph) were formed: the known 1,4,2-dithiazolidine 3 (cf. Scheme 1) and the new 1,2-thiazolidine 12 (Scheme 2). The structure of the latter was established by X-ray crystallography (Fig.1). The analogous ‘three-component reaction’ with dimethyl fumarate ( 9 ) yielded, instead of 8 , in addition to the known interception products 3 and 6 (Scheme 1), two unexpected products 15 and 16 (Scheme 3), of which the structures were elucidated by X-ray crystallography (Fig.2). Their formation is rationalized by a primary [2 + 3] cycloaddition of diazo compound 18 with 1 to give 19 , followed by a cascade of further reactions (Scheme 4).     

Beitrag zum Reaktionsmechanismus der Synthese von Seychellen [1]

New Mechanistical Details Concerning the Synthesis of Seychellen [1] In the last step of our synthesis of Seychellen ( 2 ) [1], the solvolysis of 1 , only one side-product was formed, namely 3 (Scheme 1). Now the structure of 3 has been elucidated, mainly by spectroscopic studies of its derivatives 7 and 9 (Scheme 2). In order to differentiate between two different solvolytic pathways from 1 to 3 (see Scheme 1 and 3) d₃- 1 was prepared. Solvolysis of d₃- 1 proved the mechanism shown in Scheme 1. Solvolysis of 1 and of 2-epi- 1 , respectively, furnished the same product distribution, which makes a common intermediate a very probable. In both cases 10 is an intermediate, which is slowly converted into 2 and 3 . 2-epi- 1 was prepared from 1 (Scheme 5). Kinetic measurements with 1 , d₃- 1 and 2-epi- 1 are also in agreement with the mechanism drawn in Scheme 4: k₁(72°) = (5,2±0,5) · 10^?5 sec^?1, k₁(H)/k₁(D)(72°) = 1,4±0,15; k₂(H)/k₄(H) = 0,66 and k₂(H)/k₂(D) = 2,2 if k₄(H) ≈ k₄(D) is assumed.     

Reaction of Hydroxymethyl- and Alkyl-Substituted Azulenes with Manganese Dioxide

It is shown that the 2-(hydroxymethyl)-1-methylazulenes 6 are being oxidized by activated MnO₂ in CH₂Cl₂ at room temperature to the corresponding azulene-1,2-dicarbaldehydes 7 (Scheme 2). Extension of the MnO₂ oxidation reaction to 1-methyl- and/or 3-methyl-substituted azulenes led to the formation of the corresponding azulene-1-carbaldehydes in excellent yields (Scheme 3). The reaction of unsymmetrically substituted 1,3-dimethyl-azulenes (cf. 15 in Scheme 4) with MnO₂ shows only little chemoselectivity. However, the observed ratio of the formed constitutionally isometric azulene-1-carbaldehydes is in agreement with the size of the orbital coefficients in the HOMO of the azulenes. The reaction of guaiazulene ( 18 ) with MnO₂ in dioxane/H₂O at room temperature gave mainly the expected carbaldehyde 19 . However, it was accompanied by the azulene-diones 20 and 21 (Scheme 5). The precursor of the demethylated compound 20 is the carbaldehyde 19 . Similarly, the MnO₂ reaction of 7-isopropyl-4-methyalazulene ( 22 ) as well as of 4,6,8-trimethylazulene ( 24 ) led to the formation of a mixture of the corresponding azulene-1,5-diones and azulene-1,7-diones 20 / 23 and 25 / 26 , respectively, in decent yields (Schemes 6 and 7). No MnO₂ reaction was observed with 5,7-dimethylazulene.     

Synthese und Reaktionsverhalten 2′-substituierter Isoflavone

Synthesis and Behaviour of Isoflavones Substituted in 2′-Position The protected chalcones 6–8 prepared from acetophenone and benzaldehydes rearranged to the dimethoxypropanone derivatives 9–11 in the presence of trimethyl orthoformate by Tl(NO₃)₃. 3 H₂O. These compounds could be cyclized to the isoflavones 12–14 in high yields (Scheme 2). The conversion of these isoflavones to the corresponding isoflavanes (model compounds of the phytoalexin glabridin; see Scheme 1) was the main goal of this work. Hydrogenation of 13 and 14 gave the isoflavanes 15 and 16 , respectively and their deprotection the racemic natural product 4′-O-demethylvestitol ( 17 ). Reduction of 13 and 14 yielded different compounds depending on the reducing agent (Scheme 3). The saturated alcohols 20–23 could be obtained with NaBH₄ or LiBH₄. They were transferred into the racemic 9-O-demethylmedicarpin ( 24 ) and haginin D ( 25 ) under acidic conditions. The ketones 26–28 (Scheme 4) were obtained in high yields by reduction of 12–14 with DIBAH. Deprotection of 26 yielded the racemic 2,3-dihydrodaidzein ( 29 ). Compounds 13 and 27 as well as 20 and 22 showed different behaviour under reduction conditions with Li in liquid ammonia. An efficient method for the introduction of the MeOCH₂O and the MeOCH₂CH₂OCH₂ protecting groups into hydroxylated benzaldehydes and acetophenones (Scheme 5) is described. The appropriate experimental conditions depend on the regioselectivity and on the number of the protected groups. The protected aldehydes, especially those with a protected ortho OH group, show an extraordinary ionization behaviour in chemical-ionization mass spectrometry (isobutane; Scheme 6).     

Die Struktur des Spermin-Alkaloides Aphelandrin aus Aphelandra squarrosa NEES. 170. Mitteilung über organische Naturstoffe

The structure of the spermine alkaloid aphelandrine from Aphelandra squarrosa NEES The new spermine alkaloid aphelandrine ( 2 ) has been isolated from Aphelandra squarrosa NEES . By oxidation of 2 with KMnO₄ followed by methylation (CH₂N₂) 12 and 14 could be prepared (Scheme 2). Fusion of 2 with KOH yielded spermine ( 1 ) whereas hydrolysis of 2 in hot hydrochloric acid results in lacton 17 , the structure of which could be elucidated by comparison with a synthetically prepared model compound (Scheme 3). The benzylic bonds N (10), C(11) as well as O(16), C(17) of 2 could be cleaved by hydrogenolysis (compare 23 and 26 ; Scheme 4). The elucidation of the correct linkage of the spermine moiety with the aromatic dicarboxylic acid is based mainly on chemical and spectroscopic evidence of the tetrahydro derivative 26 , the Hofmann-degradation products 28 , 30 and 31 (Scheme 6) as well as the ester 35 , prepared by partial hydrolysis of 2 (Scheme 7).     

Studies on the Adamantylation of N-Heterocycles and Nucleosides

Adamantylation of several N-heterocycles and of two ribonucleosides (uridine and toyocamycin) was studied. The exact substitution position by the adamantyl carbocation generated from adamantan-1-ol in CF₃COOH depends on the nature of the heterocyclic substrate. Thus, adamantylation of an additional exocyclic amino group (see Scheme 1), N-adamantylation of the heterocycle (Scheme 2), C-adamantylation of the heterocycle (Scheme 3), as well as the formation of heterocyclic N-adamantylcarboxamides via the Ritter reaction (Scheme 4) are possible. The structures of the reaction products were determined by means of elemental analysis and NMR, UV, and IR spectroscopy.     

The Allyl Ester as Carboxy-Protecting Group in the Stereoselective Construction of Neuraminic-Acid Glycosides

The application of the allyl-ester moiety as protecting principle for the carboxy group of N-acetylneuraminic acid is described. Peracetylated allyl neuraminate 2 is synthesized by reacting the caesium salt of the acid 1 with allyl bromide. Treatment of 2 with HCl in AcCl or with HF/pyridine gives the corresponding 2-chloro or 2-fluoro derivatives 3 and 4 , respectively (Scheme 1). In the presence of Ag₂CO₃, the 2-chloro carbohydrate 3 reacts with di-O-isopropylidene-protected galactose 5 to give the 2–6 linked disaccharide with the α-D -anomer 6a predominating (α-D /β-D = 6:1; Scheme 2). Upon activation of the 2-fluoro derivative 4 with BF₃ · Et₂O, the β-D -anomer 6b is formed preferentially (α-D /β-D = 1:5). In further glycosylations of 4 with long-chain alcohols, the β-D -anomers are formed exclusively (see 10 and 11 ; Scheme 4). The allyl-ester moiety can be removed selectively and quantitatively from the neuraminyl derivatives and the neuraminyl disaccharides by Pd(0)-catalyzed allyl transfer to morpholine as the accepting nucleophile (see Scheme 5).     

Photoinduced Molecular Transformations. Part 142. One-step syntheses of 1H-benz[f]indole-4,9-diones and 1H-indole-4,7-diones by a new regioselective photoaddition of 2-amino-1,4-naphthoquinones and 2-amino-1,4-benzoquinones with alkenes

The 2,3-dihydro-1H-benz[f]indole-4,9-diones 3a–d , h were formed in a one-step reaction in 13–82% yield by an unprecedented [3 + 2] regioselective photoaddition of 2-amino-1,4-naphthoquinone ( 1 ) with various electronrich alkenes 2 (Scheme 1, Table). The [3 + 2] photoadducts derived from 1 with vinyl ethers and vinyl acetate gave 1H-benz[f]indole-4,9-diones 4e , f , i , in 33–72% yield, by spontaneous loss of the corresponding alcohol or AcOH from the resulting adducts; 4i has a kinamycin skeleton. The [3 + 2] photoaddition also took place on irradiation of the differently substituted amino-1,4-benzoquinones 6 , 7 , and 12 and excess alkenes 2 in benzene, giving 1H-indole-4,7-dione derivatives 13 and 14 (Scheme 3), 15a and 16 (Scheme 4), and 18 (Scheme 4), respectively. The initial products in these photoadditions were proved to be hydroquinones, the air oxidation of which yielded the heterocyclic quinones; 2,3-dihydro-2-methoxy-2-methyl-5-phenyl-1H-indole-1,4,7-triyl triacetate ( 19 ) was isolated after treatment of the crude photoaddition mixture obtained from 2-amino-5-phenyl-1,4-benzoquinone ( 7 ) and 2-methoxyprop-1-ene ( 2f ) with Ac₂O and pyridine under N₂. A pathway leading to the annelated hydroquinones involving ionic intermediates arising from an electron transfer in these photoadditions is proposed (Scheme 5).     

Acid-Catalysed Dehydration of Tricyclic Unsaturated Alcohols

The tricyclic alcohols 3–7 , derived from the corresponding ketones 1 and 2 (Scheme 1), by action of acids underwent dehydration with skeletal rearrangements. Dehydration of 3 and 4 with POCl₃/pyridine (procedure A) afforded the polycyclic hydrocarbons 9, 10 , and 12, 13 , respectively. With TsOH (procedure B), on the other hand, 3 and 4 gave homo-triquinacenes 10 and 14 respectively, as well as the polycyclic ethers 11 and 15 (Scheme 2). Hydrocarbon 9 (or 12 ) was converted into 10 FSO₃H to the tertiary alcohol 16 (Scheme 4). Plausible mechanisms for these transformations are summarized in Scheme 8. Dehydration of the secondary alcohols 5 and 7 was effected by procedure A. While treatment of alcohol 5 with POCl₃/pyridine yielded two isomeric hydrocarbons 17 and 18 , similar dehydration of its epimeric alcohol 7 afforded hydrocarbon 21 as the sole product. The tertiary alcohol 6 was dehydrated by both procedures to yield two isomeric hydrocarbons 19 and 20 (Scheme 5). Hydrocarbon 20 was converted into 19 by procedure B (mechanisms, Scheme 10). Reaction of ketone 2 with CF₃COOH gave the addition product 22 converted into vinylsulfonyl fluorides 24 and 25 by treatment with FSO₃H (Scheme 6). Homo-triquinacenes 10 and 14 reacted smoothly with 4-phenyl-1,2,4-triazoline-3,5-dione to give the ‘ene’-reaction products 26 and 27 , respectively.     

Oxidative Coupling Of 2-Alkyl-6,6-dimethylpentafulvenyl Anions

Cucl₂-Induced oxidative coupling of 2-(tert-butyl)-6,6-dimethylpentafulvenyl anion 9 predominantly takes place at C(7) and C(5) to give [7–7] and [7–5] coupling products 15 and 16 in 35 and 47% yields, respectively (Scheme 3) whose structures are elucidated from 1D- and 2D-NMR analysis. Compared with the product distribution observed for 6,6-dimethylpentafulvenyl anion 2 (Scheme 1), no coupling at C(2)/C(3) of 9 is observed. This means that, besides electronic effects, steric effect are also important in oxidative couplings of fulvenyl anions. The same couplings occur in the case of 2,3-bis(6,6-dimethylfulven-2-yl)-2,3-dimethylbutane dianion 10 as well but, due to electronic as well as conformational effects (Scheme 5), intermolecular coupling (to give polymers 17 , Scheme 4) is strongly favored over intermolecular coupling. Mechanisms explaining base-catalyzed isomerization 15a ? 15b ? 15c (Scheme 6) as well as isomerization 16a ? 16b (Scheme 7) are proposed.     

Oligosaccharide Analogues of Polysaccharides

The cellobiose-derived dimer 18 , tetramer 48 , and octamer 49 have been prepared. Acetolytic debenzylation transformed the dimer 15 , obtained from the partially benzylated, dialkynylated cellobiose 2 (Scheme 1), into 16 that was deacetylated to 18 (Scheme 2), but the analogous debenzylation of the tetramer 14 proved unsatisfactory. We, therefore, avoided benzyl groups and prepared the cellobiose-derived monomer 32 by glycosidation of 27 with the crystalline trichloroacetimidates 30 or 31 (Scheme 3). The acceptor 27 was synthesised from 1,6-anhydroglucose in 7 steps (48% overall yield), and the trichloroacetimidates 30 and 31 were obtained in good overall yields from the alkynylated glucopyranoses 29 (Scheme 3). The structure of the anomeric trichloroacetimidates 30 and 31 was determined by single crystal X-ray analysis. The alkyne 34 , orthogonally C-protected by SiMe₃ and GeMe₃ groups, was transformed by a binomial strategy into the dimer 37 , the tetramer 41 , and the octamer 47 (Scheme 4). The unprotected mono- and oligomers 1 , 18 , 48 , and 49 are soluble in H₂O, MeOH, and DMSO. Their ¹H-NMR specta ((D₆)DMSO ( 1 , 18 , 48 , 49 ), CD₃OD ( 1 , 18 , 48 ), D₂O ( 49 )) show no signs of association.     

Methanofullerene Molecular Scaffolding: Towards C60-substituted poly(triacetylenes) and expanded radialenes,preparation of a C60–C70 hybrid derivative,and a novel macrocyclization reaction

The synthesis of (E)-hex-3-ene-l, 5-diynes and 3-methylidenepenta-1, 4-diynes with pendant methano[60]-fullerene moieties as precursors to C₆₀-substituted poly(triacetylenes) (PTAs, Fig. 1) and expanded radialenes (Fig. 2) is described. The Bingel reaction of diethyl (E)-2, 3-dialkynylbut-2-ene-1, 4-diyl bis(2-bromopropane-dioates) 5 and 6 with two C₆₀ molecules (Scheme 2) afforded the monomeric, silyl-protected PTA precursors 9 and 10 which, however, could not be effectively desilylated (Scheme 4). Also formed during the synthesis of 9 and 10 , as well as during the reaction of C₆₀ with thedesilylated analogue 16 (Scheme 5 ), were the macrocyclic products 11, 12 , and 17 , respectively, resulting from double Bingel addition to one C-sphere. Rigorous analysis revealed that this novel macrocyclization reaction proceeds with complete regio- and diastereoselectivity. The second approach to a suitable PTA monomer attempted N, N′-dicyclohexylcarbodiimide(DCC)-mediated esterification of (E)-2, 3-diethynylbut-2-ene-l, 4-diol ( 18 , Scheme 6) with mono-esterified methanofullerene-dicarboxylic acid 23 ; however, this synthesis yielded only the corresponding decarboxylated methanofullerene-carboxylic ester 27 (Scheme 7). To prevent decarboxylation, a spacer was inserted between the reacting carboxylic-acid moiety and the methane C-atom in carboxymethyl ethyl 1, 2-methano[60]fullerene-61, 61-dicarboxylate ( 28 , Scheme 8), and DCC-mediated esterification with diol 18 afforded PTA monomer 32 in good yield. The formation of a suitable monomeric precursor 38 to C₆₀-substituted expanded radialenes was achieved in 5 steps starting from dihydroxyacetone (Schemes 9 and 10), with the final step consisting of the DCC-mediated esterification of 28 with 2-[1-ethynyl(prop-2-ynylidene)]propane-1, 3-diol ( 33 ). The first mixed C₆₀-C₇₀ fullerene derivative 49 , consisting of two methano[60]fullerenes attached to a methano[70]fullerene, was also prepared and fully characterized (Scheme 13). The C_s-symmetrical hybrid compound was obtained by DCC-mediated esterification of bis[2-(2-hydroxy-ethoxy)ethyl] 1, 2-methano[70]fullerene-71, 71-dicarboxylate ( 46 ) with an excess of the C₆₀-carboxylic acid 28 . The presence of two different fullerenes in the same molecule was reflected by its UV/VIS spectrum, which displayed the characteristic absorption bands of both the C₇₀ and C₆₀ mono-adducts, but at the same time indicated no electronic interaction between the different fullerene moieties. Cyclic voltammetry showed two reversible reduction steps for 49 , and comparison with the corresponding C₇₀ and C₆₀ mono-adducts 46 and 30 indicated that the three fullerenes in the composite fullerene compound behave as independent redox centers.     

Reaction of 3-Amino-2H-azirines with 2-Amino-4,6-dinitrophenol (Picramic Acid): Synthesis of Quinazoline- and 1,3-Benzoxazole Derivatives

The reaction of 3-(dimethylamino)-2H-azirines 1a–c and 2-amino-4,6-dinitrophenol (picramic acid, 2 ) in MeCN at 0° to room temperature leads to a mixture of the corresponding 1,2,3,4-tetrahydroquinazoline-2-one 5 , 3-(dimethylamino)-1,2-dihydroquinazoline 6 , 2-(1-aminoalkyl)-1,3-benzoxazole 7 , and N-[2-(dimethylamino)phenyl]-α-aminocarboxamide 8 (Scheme 3). Under the same conditions, 3-(N-methyl-N-phenyl-amino)-2H-azirines 1d and 1e react with 2 to give exclusively the 1,3-benzoxazole derivative 7 . The structure of the products has been established by X-ray crystallography. Two different reaction mechanisms for the formation of 7 are discussed in Scheme 6. Treatment of 7 with phenyl isocyanate, 4-nitrobenzoyl chloride, tosyl chloride, and HCl leads to a derivatization of the NH₂-group of 7 (Scheme 4). With NaOH or NaOMe as well as with morpholine, 7 is transformed into quinazoline derivatives 5 , 14 , and 15 , respectively, via ring expansion (Scheme 5). In case of the reaction with morpholine, a second product 16 , corresponding to structure 8 , is isolated. With these results, the reaction of 1 and 2 is interpreted as the primary formation of 7 , which, under the reaction conditions, reacts with Me₂NH to yield the secondary products 5 , 6 , and 8 (Scheme 7).